Break-junction techniques provide the possibility to study electric and thermoelectric properties of single-molecule junctions in great detail. These techniques rely on the same principle of controllably breaking metallic contacts in order to create single-molecule junctions, whilst keeping track of the junction's conductance. Here, we compare results from mechanically controllable break junction (MCBJ) and scanning tunneling microscope (STM) methods, while characterizing conductance properties of the same novel mechanosensitive para- and meta-connected naphtalenophane compounds. In addition, thermopower measurements are carried out for both compounds using the STM break junction (STM-BJ) technique. For the conductance experiments, the same data processing using a clustering analysis is performed. We obtain to a large extent similar results for both methods, although values of conductance and stretching lengths for the STM-BJ technique are slightly larger in comparison with the MCBJ. STM-BJ thermopower experiments show similar Seebeck coefficients for both compounds. An increase in the Seebeck coefficient is revealed, whilst the conductance decreases, after which it saturates at around 10 µV K-1. This phenomenon is studied theoretically using a tight binding model. It shows that changes of molecule-electrode electronic couplings combined with shifts of the resonance energies explain the correlated behavior of conductance and Seebeck coefficient.
Animals can quickly adapt learned movements to external perturbations, and their existing motor repertoire likely influences their ease of adaptation. Long-term learning causes lasting changes in neural connectivity, which shapes the activity patterns that can be produced during adaptation. Here, we examined how a neural population's existing activity patterns, acquired through de novo learning, affect subsequent adaptation by modeling motor cortical neural population dynamics with recurrent neural networks. We trained networks on different motor repertoires comprising varying numbers of movements, which they acquired following various learning experiences. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural 'structure'-organization in the available population activity patterns. This structure facilitated adaptation, but only when the changes imposed by the perturbation were congruent with the organization of the inputs and the structure in neural activity acquired during de novo learning. These results highlight trade-offs in skill acquisition and demonstrate how different learning experiences can shape the geometrical properties of neural population activity and subsequent adaptation.
Adaptation, Physiological , Learning , Models, Neurological , Motor Cortex , Learning/physiology , Adaptation, Physiological/physiology , Motor Cortex/physiology , Animals , Neural Networks, Computer , Neurons/physiology , Movement/physiology , Nerve Net/physiology
The as-built roughness, or smoothness obtained during pavement construction, plays an important role in road engineering since it serves as an indicator for both the level of service provided to users and the overall standard of construction quality. Being able to predict as-built roughness is therefore important for supporting pavement design and management decision making. An as-built IRI prediction model for asphalt overlays based on profile transformation was proposed in a previous study. The model, used as basis for this work, was developed for the case of wheeled pavers without automatic screed levelling. This study presents further development of the base prediction model, including the use of an automatic screed control system through a long-distance averaging mobile reference. Formulation of linear systems that constitute the model are presented for the case of a wheeled paver using contactless acoustic sensors set-up over a floating levelling beam attached to the paver. To calibrate the model, longitudinal profile data from the Long-Term Pavement Performance SPS-5 experiment was used, obtaining a mean error of 0.17 m/km for the predicted IRI. The results obtained demonstrate the potential of the proposed approach as a modelling alternative.
Abnormalities in immune function have been described in schizophrenia but few studies have investigated cytokines in cerebrospinal fluid (CSF) and their correlation with blood levels. In this cross-sectional study, cytokines were measured in CSF and plasma of 30 subjects with schizophrenia spectrum disorder (SSD) diagnosis and 23 healthy volunteers (HV). Results showed that CSF TNFα was increased in SSD subjects compared to HV and there were no correlations between CSF and plasma cytokine levels. The present findings provide evidence of dysregulation of TNFα in CSF of schizophrenia. These results identify elevated CSF TNFα levels as a potential biomarker in schizophrenia.
Schizophrenia , Humans , Cytokines , Tumor Necrosis Factor-alpha , Cross-Sectional Studies , Biomarkers/cerebrospinal fluid
Background: Reducing maternal mortality ratio (MMR) remains a paramount goal for low- and middle-income countries (LMICs), especially after COVID-19's devastating impact on maternal health indicators. We describe our experience implementing the Hospital Padrino Strategy (HPS), a collaborative model between a high-complexity hospital (Fundación Valle del Lili) and 43 medium- and low-complexity hospitals in one Colombian department (an administrative and territorial division) from 2021 to 2022, to sustain the trend towards reducing MMR. The study aimed to assess the effects of implementing HPS on both hospital performance and maternal health indicators in Valle del Cauca department (VCD). Methods: A mixed-methods study was conducted, comprising two phases. In the first phase, we investigated a cohort of hospitals through prospective follow-up to assess the outcomes of HPS implementation on hospital performance and maternal health indicators in VCD. In the second phase, qualitative data were collected through focus groups with 131 health workers from 33 hospitals to explore the implications of the HPS implementation on healthcare personnel. All data were obtained from records within the HPS implementation and from the Health Secretary of VCD. Findings: Evidence shows that in the context of HPS, 51 workshops involved 980 healthcare workers, covering the entire territory. Substantial improvements were observed in hospital conditions and healthcare personnel's technical competencies when providing obstetric care. Seven hundred eighty-five pregnant women with obstetric or perinatal emergencies received care through telehealth systems, with a progressive increase in technology adoption. Nine percent required Intensive Care Unit (ICU) admission, and none died. The MMR decreased from 78.8 in 2021 to 12.0 cases per 100,000 live births by 2022. Improvements in indicators and conducted training sessions instilled confidence and empowerment among the healthcare teams in the sponsored hospitals, as evidenced in focus groups derived from a sample of 131 healthcare workers from 33 hospitals. Interpretation: Implementing the Hospital Padrino Strategy led to a significant MMR reduction, and consolidated a model of social healthcare innovation replicable in LMICs. Funding: The Hospital Padrino Strategy was funded by the Fundación Valle del Lili and the Health Secretary of Valle del Cauca. Furthermore, this study received funding from a general grant for research from Tecnoquimicas S.A.
The digitalization of the road transport sector necessitates the exploration of new sensing technologies that are cost-effective, high-performing, and durable. Traditional sensing systems suffer from limitations, including incompatibility with asphalt mixtures and low durability. To address these challenges, the development of self-sensing asphalt pavements has emerged as a promising solution. These pavements are composed of stimuli-responsive materials capable of exhibiting changes in their electrical properties in response to external stimuli such as strain, damage, temperature, and humidity. Self-sensing asphalt pavements have numerous applications, including in relation to structural health monitoring (SHM), traffic monitoring, Digital Twins (DT), and Vehicle-to-Infrastructure Communication (V2I) tools. This paper serves as a foundation for the advancement of self-sensing asphalt pavements by providing a comprehensive review of the underlying principles, the composition of asphalt-based self-sensing materials, laboratory assessment techniques, and the full-scale implementation of this innovative technology.
The nervous system evolved to enable navigation throughout the environment in the pursuit of resources. Evolutionarily newer structures allowed increasingly complex adaptations but necessarily added redundancy. A dominant view of movement neuroscientists is that there is a one-to-one mapping between brain region and function. However, recent experimental data is hard to reconcile with the most conservative interpretation of this framework, suggesting a degree of functional redundancy during the performance of well-learned, constrained behaviors. This apparent redundancy likely stems from the bidirectional interactions between the various cortical and subcortical structures involved in motor control. We posit that these bidirectional connections enable flexible interactions across structures that change depending upon behavioral demands, such as during acquisition, execution or adaptation of a skill. Observing the system across both multiple actions and behavioral timescales can help isolate the functional contributions of individual structures, leading to an integrated understanding of the neural control of movement.
Movement , Movement/physiology
To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n = 101) from healthy controls (n = 51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n = 97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC = 75.4%, 95% CI = 67.0-83.3%; in non-affective psychosis AUC = 80.5%, 95% CI = 72.1-88.0%, and in affective psychosis AUC = 58.7%, 95% CI = 44.2-72.0%). Test-retest reliability ranged between ICC = 0.48 (95% CI = 0.35-0.59) and ICC = 0.22 (95% CI = 0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC = 0.51 (95% CI = 0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 min, diagnostic classification of the FSA increased from AUC = 71.7% (95% CI = 63.1-80.3%) to 75.4% (95% CI = 67.0-83.3%) and phase encoding direction reliability from ICC = 0.29 (95% CI = 0.14-0.43) to ICC = 0.51 (95% CI = 0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic - but not prognostic - biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data.
Aims: Acute and chronic injuries of the interosseus membrane can result in longitudinal instability of the forearm. Reconstruction of the central band of the interosseus membrane can help to restore biomechanical stability. Different methods have been used to reconstruct the central band, including tendon grafts, bone-ligament-bone grafts, and synthetic grafts. This Idea, Development, Exploration, Assessment, and Long-term (IDEAL) phase 1 study aims to review the clinical results of reconstruction using a synthetic braided cross-linked graft secured at either end with an Endobutton to restore the force balance between the bones of the forearm. Methods: An independent retrospective review was conducted of a consecutive series of 21 patients with longitudinal instability injuries treated with anatomical central band reconstruction between February 2011 and July 2019. Patients with less than 12 months' follow-up or who were treated acutely were excluded, leaving 18 patients in total. Preoperative clinical and radiological assessments were compared with prospectively gathered data using range of motion and the abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) functional outcome score. Results: Of the 18 patients (nine male, nine female) who met the inclusion criteria, the median follow-up was 8.5 years (interquartile range (IQR) 5.6 to 10). Their mean age was 49 years (SD 11). The mean extension improved significantly from 38° (SD 15°) to 24° (SD 9°) (p = 0.027), with a mean flexion-extension arc change from 81° (SD 27°) to 93° (SD 30°) (p = 0.172) but with no forearm rotational improvement (p = 0.233) at latest follow-up. The QuickDASH functional score improved significantly from 80 (SD 14) to 52 (SD 26) following reconstruction (p = 0.031), but generally the level of disability remains high. Radiological assessment showed no progression of proximal migration of the radius, with a stable interbutton distance and ulnar variance from immediate postoperative radiograph to the latest follow-up. Conclusion: Central band interosseus membrane reconstruction using a synthetic braided cross-linked graft can improve patient-rated arm function and range of motion, but significant functional deficits remain in patients with chronic injuries.
Joint Instability , Orthopedic Procedures , Radius Fractures , Female , Humans , Male , Middle Aged , Forearm/surgery , Joint Instability/surgery , Radius/surgery , Radius Fractures/surgery , Range of Motion, Articular , Retrospective Studies , Treatment Outcome , Adult
BACKGROUND: Rifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well. METHODS: Twenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed. RESULTS: After rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers. CONCLUSIONS: There was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.
Hepatic Encephalopathy , Humans , Rifaximin/therapeutic use , Hepatic Encephalopathy/drug therapy , Cognition , Brain/diagnostic imaging , Brain/pathology , Anti-Bacterial Agents , Liver Cirrhosis/pathology
Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour.
Biological Evolution , Haplorhini , Motor Cortex , Motor Skills , Neurons , Animals , Mice , Haplorhini/physiology , Haplorhini/psychology , Motor Cortex/cytology , Motor Cortex/physiology , Motor Skills/physiology , Movement/physiology , Neural Networks, Computer , Neurons/physiology , Thinking/physiology
Neurofilament light chain protein (NfL) levels reflect neuronal damage in several neurological diseases and have been proposed as a possible biomarker. Plasma extracellular vesicles (EVs) could play an important role as mediators of the inflammatory changes associated with inducing minimal hepatic encephalopathy (MHE) in cirrhotic patients. This study investigated the association of NfL levels in plasma and EVs with the presence of MHE in cirrhotic patients, and with responses to rifaximin treatment. The NfL levels in plasma and EVs were assessed in 71 patients with liver cirrhosis (40 with MHE and 31 without MHE) and 26 controls. A total of 31 patients with MHE received rifaximin treatment. We examined changes in NfL levels in plasma and EVs before and after 6 months of rifaximin treatment. The NfL measures were correlated with cognitive alterations and plasma inflammatory cytokines. MHE patients showed increased plasma levels of NfL, which were reverted after rifaximin treatment in patients who responded to treatment. The NfL content in EVs also showed a reversal pattern in MHE patients treated with rifaximin. In multivariable analyses, NfL levels were independently associated with the presence of MHE. We also showed that patients with high levels of both ammonia and fractalkine had significantly higher NfL levels than patients with low levels of least one of these parameters. Rifaximin treatment in MHE patients showed promising results in improving axonal damage, suggesting that rifaximin may have therapeutic benefits against disease progression in MHE.
Extracellular Vesicles , Hepatic Encephalopathy , Humans , Rifaximin/therapeutic use , Hepatic Encephalopathy/drug therapy , Hepatic Encephalopathy/etiology , Intermediate Filaments , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy
Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. Design, Setting, and Participants: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. Exposure: Preoperative S aureus colonization. Main Outcomes and Measures: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. Results: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. Conclusions and Relevance: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.
Breast Neoplasms , Staphylococcal Infections , Aged , Female , Humans , Male , Breast Neoplasms/complications , Cohort Studies , Mastectomy , Staphylococcal Infections/prevention & control , Staphylococcus aureus , Surgical Wound Infection/prevention & control , Middle Aged
To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n=101) from healthy controls (n=51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n=97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC=75.4%, 95%CI=67.0%-83.3%; in non-affective psychosis AUC=80.5%, 95%CI=72.1-88.0%, and in affective psychosis AUC=58.7%, 95%CI=44.2-72.0%). Test-retest reliability ranged between ICC=0.48 (95%CI=0.35-0.59) and ICC=0.22 (95%CI=0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC=0.51 (95%CI=0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 minutes, diagnostic classification of the FSA increased from AUC=71.7% (95%CI=63.1%-80.3%) to 75.4% (95%CI=67.0%-83.3%) and phase encoding direction reliability from ICC=0.29 (95%CI=0.14-0.43) to ICC=0.51 (95%CI=0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic - but not prognostic - biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data.
We report a combined experimental and theoretical study of a series of thiomethyl (SMe) anchored cross-conjugated molecules featuring an acyclic central bridging ketone and their analogous skipped-conjugated alcohol derivatives. Studies of these molecules in a gold|single-molecule|gold junction using scanning tunneling microscopy-break junction techniques reveal a similar conductance (G) value for both the cross-conjugated molecules and their skipped-conjugated partners. Theoretical studies based on density functional theory of the molecules in their optimum geometries in the junction reveal the reason for this similarity in conductance, as the predicted conductance for the alcohol series of compounds varies more with the tilt angle. Thermopower measurements reveal a higher Seebeck coefficient (S) for the cross-conjugated ketone molecules relative to the alcohol derivatives, with a particularly high S for the biphenyl derivative 3a (-15.6 µV/K), an increase of threefold compared to its alcohol analog. The predicted behavior of the quantum interference (QI) in this series of cross-conjugated molecules is found to be constructive, though the appearance of a destructive QI feature for 3a is due to the degeneracy of the HOMO orbital and may explain the enhancement of the value of S for this molecule.
OBJECTIVE: Identification of robust biomarkers that predict individualized response to antipsychotic treatment at the early stage of psychotic disorders remains a challenge in precision psychiatry. The aim of this study was to investigate whether any functional connectome-based neural traits could serve as such a biomarker. METHODS: In a discovery sample, 49 patients with first-episode psychosis received multi-paradigm fMRI scans at baseline and were clinically followed up for 12 weeks under antipsychotic monotherapies. Treatment response was evaluated at the individual level based on the psychosis score of the Brief Psychiatric Rating Scale. Cross-paradigm connectivity and connectome-based predictive modeling were employed to train a predictive model that uses baseline connectomic measures to predict individualized change rates of psychosis scores, with model performance evaluated as the Pearson correlations between the predicted change rates and the observed change rates, based on cross-validation. The model generalizability was further examined in an independent validation sample of 24 patients in a similar design. RESULTS: The results revealed a paradigm-independent connectomic trait that significantly predicted individualized treatment outcome in both the discovery sample (predicted-versus-observed r=0.41) and the validation sample (predicted-versus-observed r=0.47, mean squared error=0.019). Features that positively predicted psychosis change rates primarily involved connections related to the cerebellar-cortical circuitry, and features that negatively predicted psychosis change rates were chiefly connections within the cortical cognitive systems. CONCLUSIONS: This study discovers and validates a connectome-based functional signature as a promising early predictor for individualized response to antipsychotic treatment in first-episode psychosis, thus highlighting the potential clinical value of this biomarker in precision psychiatry.
Antipsychotic Agents , Connectome , Psychotic Disorders , Humans , Antipsychotic Agents/therapeutic use , Connectome/methods , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/drug therapy , Treatment Outcome , Magnetic Resonance Imaging/methods , Biomarkers
Introduction. Cirrhosis is one of the ten leading causes of death in the Western hemisphere and entails a significant cost of health care. Objective. To describe the sociodemographic, clinical, and laboratory characteristics of patients older than 18 years who received care for acute decompensation of cirrhosis in the emergency services of three highly complex centers in Medellín, Colombia. Materials and methods. This was an observational retrospective cohort study from clinical records. The results were analyzed by frequency measures and represented in tables and graphics. Results. In total, 576 clinical records met the inclusion criteria; 287 were included for analysis, and 58.9% were men, with an average age of 64 (± 13.5) years. The most frequent causes of cirrhosis were alcohol intake (47.7%), cryptogenic or unspecified etiology (29.6%), and non-alcoholic fatty liver disease (9.1%). The main reasons for visiting the emergency department were the presence of edema and/or ascites (34.1%), suspicion of gastrointestinal bleeding (26.5%), abdominal pain (14.3%) and altered mental status (13.9%). The most frequent clinical manifestations of an acute decompensation of cirrhosis were ascites (45.6%), variceal hemorrhage (25.4%), hepatic encephalopathy (23.0%), and spontaneous bacterial peritonitis (5.2%). During their treatment, 56.1% of the patients received intravenous antibiotics; 24.0%, human albumin; 24.0%, vasoactive support, and 27.5%, blood products; 21.3% required management in an intensive or intermediate care unit, registering 53 deceased patients for a mortality of 18.5%. Conclusion. Patients who consult the emergency services due to acute decompensation of cirrhosis demand a high amount of health resources, frequently present associated complications, and a high percentage requires management in critical care units and shows a high in-hospital mortality rate.
Introducción. La cirrosis hace parte de las diez primeras causas de muerte en el hemisferio occidental y acarrea un importante costo en salud. Objetivo. Describir las características sociodemográficas, clínicas y de laboratorio, de los pacientes mayores de 18 años que recibieron atención por descompensación aguda de la cirrosis en los servicios de urgencias de tres centros de alta complejidad en Medellín, Colombia. Materiales y métodos. Se trata de un estudio observacional de cohorte. Los resultados se analizaron mediante medidas de frecuencia, y se representaron en tablas y gráficas. Resultados. En total, en 576 registros clínicos se cumplieron los criterios de inclusión; se incluyeron 287 para el análisis. El 58,9 % fueron hombres, con edad promedio de 64 (± 13,5) años. Las causas más frecuentes de cirrosis fueron: ingestión de alcohol (47,7 %), criptogénica o inespecífica (29,6 %) y enfermedad por hígado graso no alcohólico (9,1 %). Los principales motivos de consulta fueron: presencia de edemas, ascitis o ambas (34,1 %), sospecha de hemorragia digestiva (26,5 %), dolor abdominal (14,3 %) y alteración del estado mental (13,9 %). Los diagnósticos de complicación aguda más frecuentes fueron ascitis (45,6 %), hemorragia digestiva por várices esofágicas (25,4 %), encefalopatía hepática (23,0 %) y peritonitis bacteriana espontánea (5,2 %). El 56,1 % de los pacientes recibió antibióticos; el 24,0 %, albúmina humana; el 24,0 % medicamentos, y el 27,5 % hemoderivados. En el 21,3 % de los casos, se requirió hospitalización en la unidad de cuidados intensivos o en la de cuidados intermedios. Se registraron 53 decesos, para una mortalidad del 18,5 %. Conclusiones. Los pacientes que consultan a los servicios de urgencias por una descompensación aguda de la cirrosis demandan una gran cantidad de recursos, frecuentemente presentan complicaciones asociadas, requieren manejo en unidades de cuidado crítico y evidencian una alta tasa de mortalidad.
The implementation of a fast and efficient computer tool for field coverage studies in urban mobile radio systems is presented in this work. An accelerated and tailored ray launching method takes advantage of a ray tracing programmable framework optimized for massively parallel processing on GPUs. The PlotOptiX API is used to customize the code before applying the electromagnetic equations. The proposed code is described, and results are shown to demonstrate its correct operation. A high number of diffractions and reflections can be tracked in each ray from the transmitter to the receiver. In addition to the typical point-to-point simulation, measurement planes can also be set as receivers to provide fast predictions in wide urban areas.
There is rich variety in the activity of single neurons recorded during behaviour. Yet, these diverse single neuron responses can be well described by relatively few patterns of neural co-modulation. The study of such low-dimensional structure of neural population activity has provided important insights into how the brain generates behaviour. Virtually all of these studies have used linear dimensionality reduction techniques to estimate these population-wide co-modulation patterns, constraining them to a flat "neural manifold". Here, we hypothesised that since neurons have nonlinear responses and make thousands of distributed and recurrent connections that likely amplify such nonlinearities, neural manifolds should be intrinsically nonlinear. Combining neural population recordings from monkey motor cortex, mouse motor cortex, mouse striatum, and human motor cortex, we show that: 1) neural manifolds are intrinsically nonlinear; 2) the degree of their nonlinearity varies across architecturally distinct brain regions; and 3) manifold nonlinearity becomes more evident during complex tasks that require more varied activity patterns. Simulations using recurrent neural network models confirmed the proposed relationship between circuit connectivity and manifold nonlinearity, including the differences across architecturally distinct regions. Thus, neural manifolds underlying the generation of behaviour are inherently nonlinear, and properly accounting for such nonlinearities will be critical as neuroscientists move towards studying numerous brain regions involved in increasingly complex and naturalistic behaviours.
To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n=101) from healthy controls (n=51) in the Human Connectome Project for Early Psychosis. We also measured the test-retest (run 1 vs 2) and phase encoding direction (i.e., AP vs PA) reliability with intraclass correlation coefficients (ICC). Additionally, we measured effects of scan length on classification accuracy (i.e., AUCs) and reliability (i.e., ICCs). Finally, we tested the prognostic capability of the FSA by the correlation between baseline scores and symptom improvement over 12 weeks of antipsychotic treatment in a separate cohort (n=97). Similar analyses were conducted for the Yeo networks intrinsic connectivity as a reference. The FSA had good/excellent diagnostic discrimination (AUC=75.4%, 95%CI=67.0%-83.3%; in non-affective psychosis AUC=80.5%, 95%CI=72.1-88.0%, and in affective psychosis AUC=58.7%, 95%CI=44.2-72.0%). Test-retest reliability ranged between ICC=0.48 (95%CI=0.35-0.59) and ICC=0.22 (95%CI=0.06-0.36), which was comparable to that of networks intrinsic connectivity. Phase encoding direction reliability for the FSA was ICC=0.51 (95%CI=0.42-0.59), generally lower than for networks intrinsic connectivity. By increasing scan length from 2 to 10 minutes, diagnostic classification of the FSA increased from AUC=71.7% (95%CI=63.1%-80.3%) to 75.4% (95%CI=67.0%-83.3%) and phase encoding direction reliability from ICC=0.29 (95%CI=0.14-0.43) to ICC=0.51 (95%CI=0.42-0.59). FSA scores did not correlate with symptom improvement. These results reassure that the FSA is a generalizable diagnostic - but not prognostic - biomarker. Given the replicable results of the FSA as a diagnostic biomarker trained on case-control datasets, next the development of prognostic biomarkers should be on treatment-response data.
